Biomedical subjects

C J Pfeiffer

Publications and source records attributed to C J Pfeiffer.

At least 55 records · Page 3Linked to original sources

PubMed1989

Developmental physiology of cardiac contraction in the Japanese newt in vivo and in vitro.

Development and differentiation of whole hearts of larvae of an experimental amphibian species, the Japanese newt (Cynops pyrrhogaster), were studied in vitro and in vivo with particular reference to cardiac contraction, its temperature sensitivity and morphology. Hearts cultured in the solid or flat state in plastic flasks for 27 days developed from stage 35 to stage 55 and corresponded closely to in vivo developing hearts with respect to morphologic criteria and temperature sensitivity of cardiac contraction. The peak rate of contraction at room temperature occurred after 20 days, both for cultured hearts in vitro and for in vivo hearts, which had reached stage 50 to 52 of development. Excised fractions of heart continued to beat at reduced rates for extended periods. Hearts cultured at late stages (50 to 55) continued to beat for 282 days, though the rate decreased to 1 bpm. Although cardiac contraction rate gradually declined during long-term culture, the sensitivity of this tissue to temperature change remained constant for 250 days. Thus, culture of the heart of this species should prove useful to the investigation of factors related to induction and developmental regulation of contractility.

Animals↗

PubMed1989

Development of the heartbeat during normal ontogeny and during long-term organ culture of hearts of the newt, Cynops pyrrhogaster.

Development of cardiac contraction was investigated in the newt, Cynops pyrrhogaster, during normal development and in hearts maintained in long-term organ culture. In the embryos the heart began beating as early as stage 33. The heart rate increased up to stage 52 and then gradually decreased to the adult rate by stage 60. The heart rate showed a logarithmic temperature dependence. In organ-cultured hearts the pattern of heart rate depended on the stage at which the heart was explanted; cultured embryonic hearts showed a pattern of increase and decline similar to that seen in vivo, and hearts explanted near metamorphosis showed only a slow decline.

Animals↗

PubMed1989

Modulating action of melatonin on serotonin-induced aggravation of ethanol ulceration and changes of mucosal blood flow in rat stomachs.

Effects of melatonin and serotonin on ethanol ulceration and mucosal blood flow in the rat stomach were investigated. Melatonin and serotonin (5-HT) administration did not produce observable gastric injury in the ex vivo stomach, but the 5-HT dose dependently reduced glandular mucosal blood flow (GMBF) in this organ. Ethanol depressed GMBF and induced visible glandular mucosal injury. The latter effect was prevented by melatonin preincubation. Serotonin pretreatment aggravated the gastric mucosal injury and GMBF changes induced by ethanol; these actions were partially reversed by melatonin. The findings indicate that the GMBF and gastric injury are related; the reduction in FMBF, however, may not be the sole factor responsible for ulceration. The antagonistic effects of melatonin on 5-HT action on the stomach suggest that melatonin may act as a modulator for 5-HT action on the gastrointestinal tract.

Animals↗

PubMed1989

Gastric and cardiac organoprotection by lidocaine.

The concept of cytoprotection has been applied to many tissues afforded protection by drugs or endogenous chemicals against organelle, cyto- or histopathologic damage. We review here the "organoprotection" by lidocaine in rats and dogs as appraised by in vitro, ex vivo, and in vivo experiments with the stomach and heart, and as revealed at organelle to organ functional levels. Gastric mucosal lesions induced by 80% ethanol with 100 mM HCl on the ex vivo rat stomach were significantly reduced by lidocaine (2.2-4.4 mg/kg bolus followed by 66-132 micrograms/kg/min i. v. infusion). In anesthetized dogs with gastric corporeal lesions induced by increased gastric intraluminal pressure (50 mm Hg, 2.5 hrs), lidocaine (2.2 mg/kg bolus plus 66 micrograms/kg/min infusion) significantly reduced lesion severity. In the isolated rat heart, reperfusion after a 60 min period of ischemia induced localized cardiac mitochondrial swelling and disruption in ventricular apices which was greatly reduced if hearts were pretreated (15 min perfusion with lidocaine). In intact rats subjected to hemorrhagic shock, lidocaine pretreatment also facilitated shock resuscitation and reduced ultrastructural damage. In these diverse experiments, lidocaine organoprotection was likely mediated in part through reduction of ischemia induced organelle membrane damage and through reduction of reperfusion-induced superoxide and other oxygen-derived free radical related damage.

Animals↗

PubMed1989

Intestinal post-ischemic reperfusion injury: studies with neonatal necrotizing enterocolitis.

In the feline intestine studies have implicated superoxide (O.-) and other oxygen derived free radicals as initiators of injury as measured by increased capillary permeability during the reperfusion period. Biochemical mechanisms of this free radical generation include: xanthine oxidase dependent O.- production, hydrogen peroxide (H2O2) formation by superoxide dismutase (SOD), hydroxyl radical (OH-) production via the Haber-Weiss reaction, and lipid radical formation from membrane peroxidation. Pathological consequences of these events include inflammatory neutrophil infiltration, damage to the collagen and mucosal basement membrane, increased capillary permeability, edema, cell degeneration and necrosis. Animal models of neonatal necrotizing enterocolitis (NNEC) indicate that intestinal injury occurs after the etiologic factors (hypothermia, hypoxia) are removed. In order to determine the role of active oxygen species in the pathogenesis of NNEC, weanling hamsters and neonatal piglets were cold stressed and activities of pro/antioxidant enzymes were determined, and histopathologic and ultrastructural studies were performed. Cold stressed weanling hamsters showed a 55.7% (P less than 0.05) decrease in xanthine dehydrogenase/xanthine oxidase activity ratio. Light microscopy revealed scattered colonic mucosal erosions and submucosal edema in 50% of cold stressed animals. Transmission electron microscopy demonstrated degeneration of colonic mucosal epithelial cells, enlarged intracellular spaces, cytoplasmic vacuolization, and nuclear membrane swelling. The colonic serosa was also edematous and infiltrated with bacteria. Large intestinal tissue from cold stressed neonatal piglets showed a significant increase (P less than 0.05) in Mn and Cu, Zn, SOD, CAT, GSH-Red, total GSH, and Glc6-PD at 0 and 12 hrs. post stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Temperature-induced alterations in protein composition of newt papilloma cells.

Protein patterns of Japanese newt papilloma in vivo at low (4 degrees C), normal (10 degrees C, control) and elevated (30 degrees C) temperature were investigated by two-dimensional gel electrophoresis. There were nine protein spots in normal skin (skin specific spots: SSS) which did not exist in papillomas. At 10 degrees C, the papillomas possessed three specific protein spots (papilloma specific spots: PSS) which did not appear in normal skin. At the reduced environmental temperature, eight of the nine missing proteins in papillomas had reappeared by 12 weeks exposure. Differential responses in reappearance of SSS in papillomas varied with environmental temperature. The PSS generally were unchanged by environmental temperature modulation, although one specific protein disappeared at 12 weeks at 4 degrees C. Reappearance of normal SSS in papillomas occurred early in treatment and reflected only minor variations in high versus low temperature exposures. These data suggest that temperature-induced tumor regression may be associated with changes in protein composition.

Animals↗

PubMed1989

Comparative effects of cholera toxin, Salmonella typhimurium culture lysate, and viable Salmonella typhimurium in isolated colon segments in ponies.

Isolated segments of left dorsal colon and a side-to-side colocolostomy (between the left ventral colon and left dorsal colon) were surgically created in 6 adult ponies. Four segments, each separated by an empty segment, were inoculated (20 ml) with 1 of the following 4 solutions: phosphate buffered saline solution (PBSS)/1% polyethylene glycol (PEG); purified cholera toxin in PBSS/1% PEG (5 micrograms cholera toxin/ml of PBSS/1% PEG); lyophilized Salmonella typhimurium UCD 1755 culture lysate, reconstituted in PBSS/1% PEG; and viable S typhimurium UCD 1755 (10(8) organisms/ml of PBSS/1% PEG). Twenty hours following inoculation of the treatment solutions into the isolated colon segments, the ponies were reanesthetized. Fluid accumulation in the isolated segments was measured, and tissue samples from isolated segments were taken for examination by light microscopy and electron microscopy, and for measurement of mucosal cyclic adenosine monophosphate levels. There was fluid accumulation in segments inoculated with cholera toxin in 4 ponies (29.5 +/- 12.7 ml), and in segments inoculated with S typhimurium UCD 1755 culture lysate in 3 ponies (14.0 +/- 8.7 ml). There was no fluid accumulation in segments inoculated with either the control solution (PBSS/1% PEG) or viable S typhimurium UCD 1755. There was significantly (P less than 0.05) less cyclic adenosine monophosphate in segments inoculated with cholera toxin, Salmonella lysate, and viable Salmonella, compared with control segments. Histologically, there were minimal changes in control segments, consisting of mild to moderate submucosal edema and capillary congestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Gastrointestinal surface changes: interpretation problems and indexing possibilities (a review).

The purpose of this review on state-of-the-art and new perspectives on the use of scanning electron microscopy (SEM) in gastrointestinal pathology is to discuss the possibility of developing an index for quantitatively grading mucosal epithelial injury. This topic is reviewed within the framework of ulcer indices previously developed for gross lesions, where analogous problems exist, and in relation to the transmission electron microscope staging of epithelial cell pathology. If such an index could be developed it would increase objectivity and standardization of data analysis from laboratory to laboratory, and would allow for quantitative and statistical analysis of morphometric data. It is concluded that an index is possible based upon fields of injured cells rather than upon the grading of individual cell injury progression. An example of a useful SEM lesion index is presented. There are definite limitations to development of such an index, and guidelines are provided to help minimize some of the numerous complicating factors. These guidelines include comments on magnification, tissue contour, cell versus tissue analysis, morphometric considerations, sources of error, and other factors.

Animals↗

PubMed1989

Ultrastructural characterization of the spontaneous papilloma of Japanese newts.

The spontaneous epithelioma of the Japanese newt, Cynops pyrrhogaster, is a useful animal model for study of development and regression of papillomata of suspected viral origin. Therefore, ultrastructural studies of this cutaneous tumor were undertaken in order to characterize this model further. The ultrastructure of normal Cynops pyrrhogaster epidermis resembled teleost more than anuran epidermis. Surface cells of the bilayered stratum corneum were covered by micro-ridges and contained prominent nuclei, unlike the stratum corneum of mammals. Capillary endothelial cells contained unique small dense granules. Principal changes in tumors consisted of hyperplasia of stratum granulosum cells, increased melanin bodies in corneal cells, distorted configurations and aberrant location of outer corneal cells, which also demonstrated irregularity of micro-ridges and increased mucin and vacuole content. Intercellular spaces were enlarged between all cell types. Virus-like particles were observed in approximately 40 percent of tumors, particularly in the middle of the tumor.

Animals↗

PubMed1988

Ultrastructural aspects of equine pemphigus foliaceus-like dermatitis. Report of cases.

Pemphigus foliaceus is an uncommon dermatologic disorder occurring in several species and has been reported in horses during the past decade. An ultrastructural analysis of affected skin of horses presenting to our clinics has revealed early cytopathologic features of pemphigus-like disease, some of which closely resemble pemphigus foliaceus in the human, calve, and guinea pig. Prior to complete acantholysis and bullae formation, the intercellular spaces enlarged, but intercellular bridges and desmosomes remained intact. A novel finding was presence of aggregates of electron dense granular material which were seen in intercellular spaces of the epidermal basal cell layer, and may represent antigen-autoantibody complexed material or deranged cement substances. Other changes preceding acantholysis consisted of mild dyskeratosis, reduction of peripheral tonofilaments, enlargement of rough endoplasmic reticula, cytoplasmic vacuolization, and mitochondrial damage in epidermal cells. In more severe lesions where bullae were present and acantholysis was observed, bacterial invasion and leucocytic infiltration were evident in all epidermal layers, and corneal cells displayed cytoplasmic vacuolization and retention of nuclei. Basal cells remained intact, though intercellular spaces were enlarged on apical and lateral boundaries. The pathogenesis of this disease in the horse appeared morphologically similar to a pemphigus autoimmune disorder and its variants in other species, and morphologic evidence is provided to suggest that some cellular metabolic derangements may be concurrent with the extracellular events or cell peripheral changes that precede acantholysis and bullae formation.

Animals↗

PubMed1987

The equine colonic mucosal granular cell: identification and X-ray microanalysis of apical granules and nuclear bodies.

The granular columnar epithelial cell of the equine dorsal large colon has been studied by transmission electron microscopy and X-ray microanalysis. Particular attention was focused on nuclear bodies commonly observed as central clusters of spherical, electron-dense inclusions within the nucleus. Ultrastructural morphology as well as X-ray microanalysis spectra reveal great similarity between colonic nuclear bodies and the numerous small granules of the apical cytoplasm in these epithelial cells. X-ray spectra of these cells were distinct from those of goblet cell mucous granules and mast cell granules. No evidence was found indicating transit of nuclear body granules through the nuclear envelope, or for morphologic association with the nucleoli. Of the diverse types of nuclear bodies previously reported in other species, equine colon nuclear bodies morphologically most closely resemble those seen in rabbit adenohypophysis. Colon epithelial cell nuclear bodies are likely identical to equine small intestine nuclear bodies, but their origin and role remain unknown.

Animals↗

PubMed1987

Early ultrastructural changes in rat duodenal mucosa associated with cysteamine-induced ulcer.

The early morphologic sequelae induced by the duodenal ulcerogen, cysteamine, have been studied in rats by transmission electron microscopy. Cysteamine was administered per os at 70 mg/100 g body wt to groups of female rats sacrificed at 30 min, 1, 2, 4, 8, 12, 20, and 24 hr after chemical treatment, and duodenal tissue sampled from the antimesenteric side of the proximal duodenum, where ulcers develop, was studied. Emphasis was placed on early times as our previous scanning electron microscopic data had demonstrated enhanced in situ cellular necrosis and surface cavitation at 2-4 hr after cysteamine treatment. Results indicated intracellular changes as early as 30 min after treatment and prior to damage of the columnar cell microvilli or epithelial tight junctions. A staging of observed cellular degenerative changes suggested early apical endoplasmic reticular swelling and loss of cytoplasmic ground substance, followed later by moderate internal disruption of mitochondria. Through these stages the cell surface microvilli remained morphologically normal. Subsequently, microvilli degenerated and mitochondrial fine structure became severely disrupted and cell contents were expelled. Deeper villous changes such as separation of columnar cells from the lamina propria and alterations of selected elements within the lamina propria were observed. These data suggest that intracellular cytotoxic reactions at the villous tips occur early and may precede the influence of intraluminal damaging factors induced by cysteamine.

Animals↗

PubMed1987

Topographic localization of gastric lesions and key role of plasma bicarbonate concentration in dogs with experimentally induced gastric dilatation.

The canine gastric response to acute dilatation, its correlation with selected systemic cardiovascular changes, and preliminary study of its modulation by membrane-stabilizing agents were studied in 21 Beagle dogs. Gastric mucosal damage and adverse cardiovascular sequelae were induced by inflation of an intragastric balloon to 60 mm of Hg in each anesthetized dog for 2.5 hours. At this time, dogs were given 1 of 4 treatments: control; lidocaine HCl, 2.2 mg bolus + 66 micrograms/min, IV; prednisolone succinate, 6.6 mg, IV; and zinc sulfate, 2.2 mg bolus + 66 micrograms/min, IV. After treatments were given, there was a 4-hour deflation period. Throughout the 6.5 hours, continuous measurements were made of stroke volume, arterial blood pressure, PaO2, PaCO2, and plasma HCO3- concentration. Gastric lesions, assessed by planimetric analysis of ulcer indices, were limited to the fundus and corpus and were significantly decreased by lidocaine administration. As seen by histopathologic examination, a sharply delineated transverse area bordering the corporeal-antral junction near the lesser curvature demonstrated minimal resistance to ulceration and showed mucus depletion. Plasma HCO3- concentration, base excess, and CO2 values were negatively correlated with development of gastric damage, indicating that plasma HCO3- concentration has a key role in mucosal resistance to ulcerogenesis.

Animals↗

PubMed1987

Development of cysteamine-induced ultrastructural surface changes on duodenal mucosa.

Duodenal ulcers were induced acutely in female rats by a single oral administration of cysteamine, 70 mg/100 gm, in order to study morphologic progression of lesion development from the perspective of cellular surface changes by scanning electron microscopy. Thick sections of resin-embedded specimens were also studied by light microscopy, and animals were sacrificed at intervals of 30 minutes, 1, 2, 4, 8, 12, 20, and 24 hours post-treatment. Earliest evidence of cytologic lesions was apparent at 2 hours and data confirmed earlier reports that alterations began at villous tips. Both cellular sloughing and in situ cellular injury were evident, the latter phenomenon constituting the principal mode of cysteamine-induced erosion. In situ change began, from surface perspective, as a minute cavitation on the apical aspect of an isolated, single epithelial cell which was surrounded by normal cells. These early lesions progressed to in situ necrosis either of isolated cells or of small clusters of adjacent cells. This phenomenon occurred concurrently on multiple villi, all within the localized site at which cysteamine-induced duodenal ulcers are known to develop. An additional early morphologic change was the occasional appearance of a background of pleomorphic cellular apices of variable size on the villous ridges. By 8 to 12 hours, cellular damage advanced to erosions with some cells in the preulcer area still showing initial stages of in situ cellular injury. Precipitated mucus on the surface was increased in the preulcer area, and by 20 to 24 hours typical duodenal ulcers were evident. These scanning electron microscopic data confirm the significance of surface damage at villous tips very early in the cysteamine-induced ulcerogenesis. The present higher resolution findings demonstrated that earliest cellular damage, principally in situ cell injury, occurred simultaneously at multiple sites in the preulcer zone rather than at a single cluster of cellular damage which enlarges peripherally.

Animals↗

PubMed1987

Anti-ulcer and membrane stabilizing actions of zinc acexamate.

The effects of zinc acexamate on stress and reserpine ulcers as well as on gastric mast cells degranulation and membrane stability were evaluated in the rat. Zinc acexamate (100 mg/kg) has demonstrated an inhibitory effect on cold-restraint stress and reserpine-induced ulcer in a dose-dependent manner. Pretreatment of rats, prior to cold restraint stress, reduced gastric mast cell degranulation. Zinc acexamate (10(-4) M) inhibits Triton X-100 release of beta-glucuronidase in isolated hepatic lysosomes. These observations suggest that ulcer protective actions of zinc acexamate may be exerted in part through enhancing gastric mucosal resistance by stabilizing biological membrane integrity.

Aminocaproates↗

PubMed1987

Enteric serosal surface in the piglet. A scanning and transmission electron microscopic study of the mesothelium.

The ultrastructure of the serosal mesothelium of the stomach, and small and large intestine has been investigated for the first time by scanning and transmission electron microscopy in the normal piglet. Its fine structure is similar to that reported previously for the calf and rat visceral mesothelium and is notable for the presence of abundant, long, widely spaced microvilli extending from the apical surface of mesothelial cells. Large rough endoplasmic reticula, free ribosomes, and pinocytotic vesicles were numerous, but Golgi apparatuses, mitochondria, lysosomes, and other intracellular inclusions were scarce. Little difference was observed between the serosal mesothelium of the three regions investigated. This information on the normal piglet mesothelium may be useful for future studies of pathogenesis of experimentally induced peritoneal adhesions, since the immature animal is at elevated risk and the porcine digestive tract resembles that of the human.

Animals↗

PubMed1985

Teratogenic effects of carcinogenic agents on limb regeneration in the Japanese newt Cynops pyrrhogaster.

Normal regeneration of the amputated forelimb of the Japanese newt Cynops pyrrhogaster and regeneration after a single intraperitoneal injection of three potent mutagenic/carcinogenic agents was investigated. Three dose levels of each agent and controls were tested for teratogenicity in this newt model with the following chemicals: N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 4-nitro-quinoline-1-oxide, and 2-(2-furyl)-3-(5-nitrofuryl)acrylamide. These chemicals were administered at 10 days (late dedifferentiation stage), 20 days (late bud stage), and 30 days (early digits stage) after amputation at the midforelimb. A total of 628 newts, with 16-20 animals per group, were used. Normal forelimb regeneration in Cynops pyrrhogaster closely paralleled that reported for other species. A variety of deformities, including syndactyly, polydactyly, oligodactyly, brachydactyly, and digital branching, were occasionally observed in control regenerating forelimbs, with syndactyly occurring at highest incidence (17.5%). All three mutagens at all tested dose levels enhanced the incidence of teratogenic changes, though increases were not always statistically significant. MNNG, particularly when administered at the time of initial chondrogenesis (20 days, late bud stage), was especially teratogenic. The type of forelimb deformity was not mutagen-specific in this experiment. As Cynops pyrrhogaster is easily and inexpensively maintained and tolerates surgery well, this model with the regenerating forelimb should prove useful for further studies on teratogen screening. Also, studies directed toward mutagenic and epigenetic effects of exogenous agents on rapidly proliferating and differentiating tissues can be investigated with this model, which obviates transplacental excursion and metabolism of test compounds.

4-Nitroquinoline-1-oxide↗

PubMed1985

Dietary factors and the incidence of cancer of the stomach.

A case-control study of diet and stomach cancer was conducted during 1979-1982 in Toronto, Winnipeg, and St. John's Canada. Two hundred forty-six histologically verified cancer cases were individually matched by age, sex, and area of residence to 246 randomly selected population controls. Daily nutrient consumption values were calculated from quantitative diet history questionnaire data through use of the US Department of Agriculture Food Composition Data Bank, which was extended and modified for Canadian items. For the analysis, continuous conditional logistic regression methods were used. It was found that consumption of dietary fiber was associated with decreased risk of gastric cancer; the odds ratio estimate of trend was 0.40/10 g average daily intake of fiber (i.e., 0.40(1.5)/15 g, etc.) (p less than 10(-8)). Also, average daily consumption of nitrite, chocolate, and carbohydrate was associated with increasing trends in risk, with odds ratio estimates, respectively, 2.6/mg (p less than 10(-4)), 1.8/10 g (p less than 10(-4)), and 1.5/100 g (p = 0.015). While citrus fruit intake appeared to be somewhat protective (odds ratio = 0.75/100 g daily average, p = 0.0056), vitamin C intake was less so, and vitamin E not at all. Thus, a number of dietary components seem to be implicated in the pathogenesis of stomach cancer.

Adult↗